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Coupled folding and binding with alpha-helix-forming molecular recognition elements.

Christopher J Oldfield·Yugong Cheng·Marc S Cortese·Pedro Romero·Vladimir N Uversky·A Keith Dunker
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Abstract

Many protein-protein and protein-nucleic acid interactions involve coupled folding and binding of at least one of the partners. Here, we propose a protein structural element or feature that mediates the binding events of initially disordered regions. This element consists of a short region that undergoes coupled binding and folding within a longer region of disorder. We call these features "molecular recognition elements" (MoREs). Examples of MoREs bound to their partners can be found in the alpha-helix, beta-strand, polyproline II helix, or irregular secondary structure conformations, and in various mixtures of the four structural forms. Here we describe an algorithm that identifies regions having propensities to become alpha-helix-forming molecular recognition elements (alpha-MoREs) based on a discriminant function that indicates such regions while giving a low false-positive error rate on a large collection of structured proteins. Application of this algorithm to databases of genomics and functionally annotated proteins indicates that alpha-MoREs are likely to play important roles protein-protein interactions involved in signaling events.

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Binding SitesDatabases, ProteinKineticsModels, MolecularModels, TheoreticalProtein BindingProtein ConformationProtein FoldingProtein Structure, SecondaryProteinsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Christopher J Oldfield, Yugong Cheng, Marc S Cortese, Pedro Romero, Vladimir N Uversky, A Keith Dunker. 2005-09-20. Coupled folding and binding with alpha-helix-forming molecular recognition elements.. https://doi.org/10.1021/bi050736e

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